Background

Intestinal fibrosis, which is caused by excessive extracellular matrix deposition, is a common complication of inflammatory bowel disease. Macrophages assume a wide spectrum of different functional phenotypes (M1, M2a, M2b, and M2c) that differ in the expression of surface proteins, transcription factors, and cytokine production. It is believed that macrophages contribute to all phases of repair, inflammation, proliferation, and remodelling through their progression from M1 to M2c. We have demonstrated that STAT6 (-/-) mice exhibit an impaired M2a polarisation and delayed wound healing in an acute model of colitis. We have hypothesised that these animals are more susceptible to fibrosis development in response to chronic bowel damage.

Methods

WT or STAT6 (-/-) mice were given TNBS (0.5, 0.5, 0.75, 0.75, 1, and 1 mg, intrarectally) or saline weekly, and body weight was recorded daily. Seven days after the last dose, the mice were sacrificed, and the expression of markers of fibrosis (Vimentin, COL1A1,α-SMA, MMP2, FSP-1, and TIMP-1), macrophage markers (CD206, CD16, and CD86), and STAT3 were analysed in colonic tissue by qPCR (results are expressed as fold induction vs vehicle-treated animals).